Pierelli L, Scambia G, Fattorossi A, Bonanno G, Battaglia A, Perillo A, Menichella G, Panici P B, Leone G, Mancuso S
Cattedra di Ematologia, Catholic University, Rome, Italy.
Br J Cancer. 1998 Oct;78(8):1024-9. doi: 10.1038/bjc.1998.622.
We evaluated the protective ability of amifostine on peripheral blood mononuclear cell (PBMC)-derived colony-forming unit (CFU) and PB CD34+ cells which were previously exposed in vitro to etoposide, carboplatin, doxorubicin and taxotere. Amifostine pretreatment protected PBMC-derived CFU from the toxic effect of etoposide, carboplatin and taxotere. A significant detrimental effect was exerted by amifostine on the growth of doxorubicin-treated PBMC-derived CFU. Liquid cultures of PB CD34+ cells reproduced faithfully the effects observed on growth of PBMC-derived CFU and confirmed amifostine chemoprotection against etoposide and carboplatin with its detrimental effect on doxorubicin-treated progenitors. Combining the data of viable cell count, cytometric estimation of apoptosis, cell cycle and viable cell replication rate, we found that amifostine protects from etoposide and carboplatin toxicity mainly through a mechanism of cell rescue. Conversely, the detrimental effect of amifostine on the growth of doxorubicin-treated PB CD34+ cells is apparently due to an increased G2/M arrest. In conclusion, amifostine protects haematopoietic progenitors from etoposide, carboplatin and taxotere. Progenitor rescue is the mechanism through which amifostine reduced etoposide and carboplatin toxicity.
我们评估了氨磷汀对体外预先暴露于依托泊苷、卡铂、多柔比星和多西他赛的外周血单个核细胞（PBMC）衍生的集落形成单位（CFU）和外周血CD34+细胞的保护能力。氨磷汀预处理可保护PBMC衍生的CFU免受依托泊苷、卡铂和多西他赛的毒性作用。氨磷汀对多柔比星处理的PBMC衍生的CFU的生长产生了显著的有害影响。PB CD34+细胞的液体培养忠实地再现了对PBMC衍生的CFU生长所观察到的影响，并证实了氨磷汀对依托泊苷和卡铂的化学保护作用及其对多柔比星处理的祖细胞的有害影响。结合活细胞计数、细胞凋亡的流式细胞术估计、细胞周期和活细胞复制率的数据，我们发现氨磷汀主要通过细胞挽救机制保护细胞免受依托泊苷和卡铂的毒性。相反，氨磷汀对多柔比星处理的PB CD34+细胞生长的有害影响显然是由于G2/M期阻滞增加所致。总之，氨磷汀可保护造血祖细胞免受依托泊苷、卡铂和多西他赛的影响。祖细胞挽救是氨磷汀降低依托泊苷和卡铂毒性的机制。
